Differential effect of everolimus on progression of early and late cardiac allograft vasculopathy in current clinical practice.

Randomized trials showed that mTOR inhibitors prevent early development of cardiac allograft vasculopathy (CAV). However, the action of these drugs on CAV late after transplant is controversial, and their effectiveness for CAV prevention in clinical practice is poorly explored. In this observational study we included 143 consecutive heart transplant recipients who underwent serial intravascular ultrasound (IVUS), receiving either everolimus or mycophenolate as adjunctive therapy to cyclosporine. Ninety-one recipients comprised the early cohort, receiving IVUS at weeks 3-6 and year 1 after transplant, and 52 the late cohort, receiving IVUS at years 1 and 5 after transplant. Everolimus independently reduced the odds for early CAV (0.14 [0.01-0.77]; p = 0.02) but it did not appear to influence late CAV progression. High-dose statins were found to be associated with reduced CAV progression both early and late after transplant (p ≤ 0.05). Metabolic abnormalities, such as high triglycerides, were associated with late, but not with early CAV progression. By highlighting a differential effect of everolimus and metabolic abnormalities on early and late changes of graft coronary morphology, this observational study supports the hypothesis that everolimus may be effective for CAV prevention but not for CAV treatment, and that risk factors intervene in a time-dependent sequence during CAV development.

Changes in exercise capacity induced by heart transplantation: prognostic and therapeutic implications.

Survival and exercise performance are key targets of heart transplantation (HT). We designed this study to help in identifying (1) patients with chronic heart failure (CHF) at risk of poor exercise capacity after HT and (2) HT recipients presenting risk factors modifiable with exercise showing a potential impact on outcome. We enrolled 49 HT recipients (age 52 ± 12 years, 84% males) who underwent a cardiopulmonary exercise test before (9 ± 6 months) and after (20 ± 14 months) HT. In the CHF phase, lower peak oxygen consumption (VO(2) ) (odds ratio 0.69, P=0.017) independently predicted peak VO(2) improvement after HT. In the post-HT phase, body mass index (BMI) [adjusted hazard ratio (HR) 1.16, P=0.034] and VE (ventilation)/VCO(2) (carbon dioxide production) slope (adjusted HR 1.07, P=0.031) independently predicted mortality. In conclusion, CHF patients with only a moderate impairment of peak VO(2) are at a risk of failing to achieve a significant improvement of exercise performance after HT. In the post-HT phase, a BMI≥28 and/or a VE/VCO(2) slope ≥47 represent risk factors for death, which are potentially modifiable with exercise. Prospective randomized studies are needed to analyze the effects of training on functional capacity and outcome in the different subsets of HT recipients.

Expenditure and value for money: the challenge of implantable cardioverter defibrillators.

Many technology-driven interventions entail considerable financial cost, raising affordability issues. The implantable cardioverter defibrillator (ICD) is a case of an effective primary prevention intervention with high initial costs that is capable of delivering long-term population benefits. At first glance, such interventions may provoke diffidence, if not active resistance, due to the financial burdens which inevitably accompany their widespread adoption. In this article, we review the available economic tools that can help address the ICD cost issue. We think awareness of such knowledge may facilitate dialogues between physicians, administrators and policymakers, and help foster rational decision-making.

Optimisation of therapeutic strategies for ST-segment elevation acute myocardial infarction: the impact of a territorial network on reperfusion therapy and mortality.

OBJECTIVE: To assess the clinical impact of a regional network for the treatment of ST-segment elevation myocardial infarction (STEMI). METHODS: All patients with STEMI (n = 1823) admitted to any of the hospitals of an area with one million inhabitants during the year 2002 (n = 858)-that is, before the network was implemented, and in 2004 (n = 965), the year of full implementation of the network, were enrolled in this study. The primary evaluation was in-hospital mortality. Secondary outcomes included the incidence of major adverse cardiac and cerebrovascular events (MACCE), defined as death, myocardial infarction, stroke and coronary revascularisation procedures over 1-year follow-up. RESULTS: Between 2002 and 2004, there was a major change in reperfusion strategy: primary angioplasty increased from 20.2% to 65.6% (p<0.001), fibrinolytic therapy decreased from 38.2% to 10.7% (p<0.001) and the rate of patients not undergoing reperfusion was reduced from 41.6% to 23.7% (p<0.001). In-hospital mortality decreased from 17.0% to 12.3% (p = 0.005), and this reduction was sustained at 1-year follow-up (23.9% in 2002 and 18.8% in 2004, p = 0.009). Similarly, the 1-year incidence of all MACCE was reduced from 39.5% in 2002 to 34.3% in 2004 (p = 0.01). CONCLUSIONS: Organisation of a territorial network for STEMI is associated with increased rates of reperfusion therapy and reduction of in-hospital and 1-year mortality.

Prevalence of substance-related disorders in heart transplantation candidates.

Substance abuse cessation is one of the leading factors in determining the eligibility for the heart transplantation waiting list, as noncompliance with this issue may seriously endanger posttransplantation outcomes. Yet, the prevalence of substance-related disorders among candidates for heart transplantation has not been evaluated enough. Eighty three heart transplantation candidates were assessed for prior or current substance-related disorders through the Structured Clinical Interview for mental disorders according to DSM-IV. A prior history of at least one substance-related disorder was found in 64% of patients, with nicotine dependence as the most prevalent diagnosis (61.4% of the sample). Ten subjects were currently smokers, despite heart failure. A prior history of alcohol abuse and caffeine intoxication was found in 9.6% and 2.4% of patients, respectively. Substance abuse or dependence behaviors should be monitored during all the phases of heart transplantation program. Early identification of current substance-related disorders may allow better allocation of organ resources and proper lifestyle modification programs provision. A prior history of substance-related disorders should alert physicians to assess patients for possible relapse, especially after transplantation. The inclusion of a specialist in the assessment and treatment of substance-related disorders in the heart transplantation unit may reduce the risk of unsuccessful outcomes due to noncompliance with an adequate lifestyle.

Electrical cardioversion for persistent atrial fibrillation or atrial flutter in clinical practice: predictors of long-term outcome.

Despite the results of Atrial Fibrillation Follow-up Investigation of Rhythm Management and Rate Control versus Electrical Cardioversion for Persistent Atrial Fibrillation trials, which favour a general shift in atrial fibrillation (AF) therapeutic approach towards control of ventricular rate, a strategy based on restoration of sinus rhythm could still play a role in selected patients at lower risk of AF recurrence. We explored possible predictors of relapses after external electrical cardioversion among patients with persistent AF or atrial flutter (AFL). We analysed the clinical characteristics and conventional echocardiographic parameters of patients with persistent AF/AFL enrolled in an institutional electrical cardioversion programme. Among 242 patients (AF/AFL, 195/47; mean age 62+/-13 years), sinus rhythm was restored in 215 (89%) and maintained in 73 (34%) at a follow-up of 930 days (median). No baseline clinical/echocardiographic variables predicted acute efficacy of cardioversion at logistic regression analysis. However, two variables predicted long-term AF/AFL recurrence among patients with successful cardioversion at multivariate Cox's proportional hazards analysis: (i) duration of arrhythmia>or=1 year (HR, 2.07; 95% CI, 1.29-3.33) and (ii) presence of previous cardioversion (HR, 1.67; 95% CI, 1.17-2.38). These variables also presented high-positive predictive values (72% and 80% respectively). Whereas the high acute efficacy of electrical cardioversion (approximately 90%) does not appear to be predictable, two simple clinical variables could help identify patients at higher risk of long-term AF/AFL recurrence after successful electrical cardioversion. We think there could be a case for initially attempting external electrical cardioversion to patients who have had AF/AFL for <1 year. In such patients, the chance of long-term success appears to be relatively high.

Wide spectrum of presentation and variable outcomes of isolated left ventricular non-compaction.

OBJECTIVES: To investigate diagnostic routes, echocardiographic substrates, outcomes and prognostic factors in patients with isolated ventricular non-compaction (IVNC) identified by echocardiographic laboratories with referral from specialists and primary care physicians. PATIENTS AND DESIGN: Since 1991, all patients with suspected IVNC were flagged and followed up on dedicated databases. Patients were divided into symptom-based and non-symptom-based diagnostic subgroups. RESULTS: 65 eligible patients were followed up for 6-193 months (mean 46 (SD 44). In 53 (82%) patients, IVNC was associated with variable degrees of left ventricular (LV) dilatation and hypokinesia, and in the remaining 12 (18%) LV volumes were normal. Diagnosis was symptom based in 48 (74%) and non-symptom based in 17 (26%) (familial referral in 10). The non-symptom-based subgroup was characterised by younger age, lower prevalence of ECG abnormalities, better systolic function and lower left atrial size, whereas the extent of non-compaction was not different. No major cardiovascular events occurred in the non-symptom-based group, whereas 15 of 48 (31%) symptomatically diagnosed patients experienced cardiovascular death or heart transplantation (p = 0.01, Kaplan-Meier analysis). Independent predictors of cardiovascular death or heart transplantation were New York Heart Association class III-IV, sustained ventricular arrhythmias and left atrial size. CONCLUSIONS: IVNC is associated with a broad spectrum of clinical and pathophysiological findings, and the overall natural history and prognosis may be better than previously thought. Adult patients with incidental or familial discovery of IVNC have an encouraging outlook, whereas those who have symptoms of heart failure, a history of sustained ventricular tachycardia or an enlarged left atrium have an unstable course and more severe prognosis.

Clinical value of multidetector CT coronary angiography as a preoperative screening test before non-coronary cardiac surgery.

OBJECTIVE: Myocardial scintigraphy and/or conventional angiography (CA) are often performed before cardiac surgery in an attempt to identify unsuspected coronary artery disease which might result in significant cardiac morbidity and mortality. Multidetector CT coronary angiography (MDCTCA) has a recognised high negative predictive value and may provide a non-invasive alternative in this subset of patients. The aim of this study was to evaluate the clinical value of MDCTCA as a preoperative screening test in candidates for non-coronary cardiac surgery. METHODS: 132 patients underwent MDCTCA (Somatom Sensation 16 Cardiac, Siemens) in the assessment of the cardiac risk profile before surgery. Coronary arteries were screened for > or = 50% stenosis. Patients without significant stenosis (Group 1) underwent surgery without any adjunctive screening tests while all patients with coronary lesions > or = 50% at MDCTCA (Group 2) underwent CA. RESULTS: 16 patients (12.1%) were excluded due to poor image quality. 72 patients without significant coronary stenosis at MDCTCA were submitted to surgery. 30 out of 36 patients with significant (> or = 50%) coronary stenosis at MDCTCA and CA underwent adjunctive bypass surgery or coronary angioplasty. In 8 patients, MDCTCA overestimated the severity of the coronary lesions (> 50% MDCTCA, < 50% CA). No severe cardiovascular perioperative events such as myocardial ischaemia, myocardial infarction or cardiac failure occurred in any patient in Group 1. CONCLUSIONS: MDCTCA seems to be effective as a preoperative screening test prior to non-coronary cardiac surgery. In this era of cost containment and optimal care of patients, MDCTCA is able to provide coronary vessel and ventricular function evaluation and may become the method of choice for the assessment of a cardiovascular risk profile prior to major surgery.

Long-term safety and effectiveness of statins for heart transplant recipients in routine clinical practice.

BACKGROUND: Whereas the efficacy of statins after heart transplantation (HT) in controlled study settings has been clearly demonstrated, more extensive data are required on the safety and effectiveness of long-term treatment in routine clinical practice. METHODS: We analyzed the risks and benefits in clinical practice of treatment with statins in all patients who survived HT for at least a month from December 1985 through 2001. RESULTS: During a mean follow-up of 4.8+/-3.8 years, 186 patients were treated with statins (for a median duration [25th to 75th percentile] of 29 [12 to 54] months), while 48 received dietary therapy alone. Patients treated with statins (pravastatin, 48%; atorvastatin, 37%; simvastatin, 14%) presented linearized rates of rhabdomyolisis, myositis, and significant transaminase elevation of 0.37%, 0.74%, and 0.37% per year of treatment, respectively (no fatal event occurred). Low-density lipoprotein decreased after statins by 19% (P<.001). At multivariate analysis, treatment with statins was independently associated with reduced risk of cardiac allograft vasculopathy and overall mortality (P<.001). CONCLUSIONS: Our data provide necessary confirmation of the safety and effectiveness in routine clinical practice of appropriately monitored long-term administration of statins (particularly atorvastatin, pravastatin, and simvastatin) in the chronic post-HT phase. Strict follow-up is needed for HT recipients receiving high doses of statins with/without other medications potentially exacerbating the risk of adverse effects.

Non-invasive evaluation of the myocardial substrate of cardiac amyloidosis by gadolinium cardiac magnetic resonance.

OBJECTIVE: To investigate the prevalence and distribution of gadolinium (Gd) enhancement at cardiac magnetic resonance (CMR) imaging in patients with cardiac amyloidosis (CA) and to look for associations with clinical, morphological, and functional features. PATIENTS AND DESIGN: 21 patients with definitely diagnosed CA (nine with immunoglobulin light chain amyloidosis and 12 transthyretin related) underwent Gd-CMR. RESULTS: Gd enhancement was detected in 16 of 21 (76%) patients. Sixty six of 357 (18%) segments were enhanced, more often at the mid ventricular level. Transmural extension of enhancement within each patient significantly correlated with left ventricular (LV) end systolic volume (r = 0.58). The number of enhanced segments correlated with LV end diastolic volume (r = 0.76), end systolic volume (r = 0.6), and left atrial size (r = 0.56). Segments with > 50% extensive transmural enhancement more often were severely hypokinetic or akinetic (p = 0.001). Patients with > 2 enhanced segments had significantly lower 12 lead QRS voltage and Sokolow-Lyon index. No relation was apparent with any other clinical, morphological, functional, or histological characteristics. CONCLUSION: Gd enhancement is common but not universally present in CA, probably due to expansion of infiltrated interstitium. The segmental and transmural distribution of the enhancement is highly variable, and mid-ventricular regions are more often involved. Enhancement appears to be associated with impaired segmental and global contractility and a larger atrium.

Autocrine and intracrine signaling for cardiogenesis in embryonic stem cells: a clue for the development of novel differentiating agents.

Cardiogenesis, one of the earliest and most complex morphogenetic events in the embryo, is not fully understood at the molecular level and is typically a low-yield process. Affording a high throughput of cardiogenesis from a suitable population of pluripotent cells is therefore a major assignment in the perspective of a stem cell therapy for heart failure. Analysis of cardiac lineage commitment in mouse embryonic stem cells and in vivo models of cardiac differentiation revealed that a number of crucial growth factors are released from precursor cells, acting in an autocrine fashion on specific plasma membrane receptors to prime a cardiogenic decision. Nevertheless, it is increasingly becoming evident that cell nuclei harbor the potential for intrinsic signal transduction pathways. The term "intracrine" has been proposed for growth regulatory peptides that have been shown to act within their cell of synthesis at the level of the nuclear envelope, chromatin, or other subnuclear components. Considerable evidence links known intracrines with transcriptional responses and self-sustaining loops that behave as long-lived signals and impart features characteristic of differentiation, growth regulation and cell memory. This review focuses on a number of autocrine and intracrine systems within the context of cardiac differentiation and emphasizes the identification of cardiogenic mechanisms as a clue for the development of unprecedented differentiating strategies. In this regard, recently synthesized mixed esters of hyaluronan with butyric and retinoic acid primed the expression of cardiogenic genes and elicited a remarkable increase in cardiomyocyte yield in mouse embryonic stem cells. This demonstrates the potential for chemically modifying the gene program of cardiac differentiation without the aid of gene transfer technologies and sets the basis for the design of a novel generation of chemicals suited for the organization of targeted lineage patterning in stem cells.

Interleukin-6 gene polymorphism is an age-dependent risk factor for myocardial infarction in men.

Several studies show that inflammatory components may contribute to atherosclerosis and increase the risk for myocardial infarction (MI). Interleukin-6 (IL-6) is a key pro-inflammatory and immune-modulatory cytokine of relevance for cardiovascular diseases. In this case-control study, 200 patients with MI and 257 healthy controls were genotyped for the polymorphism present in -174 promoter region of the IL-6 gene. Plasma concentrations of IL-6 and C-reactive protein (CRP) in a group of patients and controls were measured. The -174 C allele was associated with an increased risk of developing MI (OR = 2.886, c.i. = 1.801-4.624, P = 0.0001) in older patients, while no association was found in younger ones. The IL-6 plasma levels were higher in patients with MI carrying the CC genotype than in GG patients (CC carriers, IL-6 = 2.97 pg mL(-1) vs. GG carriers = 1.81 pg mL(-1), P = 0.016). A positive correlation of IL-6 levels with those of CRP in serum from patients with MI was also found. Data from this study suggest that the C allele of the promoter polymorphism in the IL-6 gene is a risk factor for MI in the elderly, and the production of the IL-6 is differentially affected by different genotypes of the IL-6 -174 promoter polymorphism.

Pulmonary arterial hypertension associated to connective tissue diseases.

Pulmonary arterial hypertension is a well-known complication of connective tissue diseases such as systemic sclerosis, systemic lupus erythematosus, mixed connective tissue diseases, and to a lesser extent, rheumatoid arthritis, dermatopolymyositis and primary Sjögren's syndrome. In these patients, pulmonary hypertension may occur in association with left heart disease, interstitial fibrosis or as a result of a isolated pulmonary arteriopathy. The incidence of pulmonary arterial hypertension in the limited form of systemic sclerosis is about 10%. The pathophysiologic mechanisms leading to pulmonary arterial hypertension remain unknown. Symptoms and clinical presentation are very similar to idiopathic pulmonary arterial hypertension but mortality was confirmed to be higher. Echocardiography is the reference investigation for the detection of pulmonary arterial hypertension but the results should be confirmed by right heart catheterization. Treatment appears more complex as compared to idiopathic pulmonary arterial hypertension. Intravenous epoprostenol therapy has been shown to be effective in a special trail. Also, the endothelin receptor antagonists bosentan and sitaxentan, the phosphodyesterase-type-5 sildenafil and subcutaneous treprostinil have shown favourable results.

32P brachytherapy in the treatment of complex Cypher in-stent restenosis.

Treatment of in-stent restenosis after implantation of a drug-eluting stent is a critical issue. We provide the first report of the use of intravascular radiation therapy for this purpose in a 73-year-old diabetic patient stented for small-vessel bifurcation; treatment of Cypher diffuse in-stent restenosis with (32)P brachytherapy proved successful at clinical and angiographic follow-up at 7 months. This finding should encourage systematic studies on the safety and efficacy of IRT in this problematic setting.

Long term outcome in patients with silent versus symptomatic ischaemia during dobutamine stress echocardiography.

OBJECTIVES: To compare the long term prognosis of patients having silent versus symptomatic ischaemia during dobutamine stress echocardiography (DSE). DESIGN: Observational study. SETTING: Tertiary referral centre. PATIENTS: 931 patients who experienced stress induced myocardial ischaemia during DSE. RESULTS: Silent ischaemia was present in 643 of 931 patients (69%). The number of dysfunctional segments at rest (mean (SD) 9.6 (5.1) v 8.8 (5.0), p = 0.1) and of ischaemic segments (3.5 (2.2) v 3.8 (2.1), p = 0.2) was comparable in both groups. During a mean (SD) follow up of 5.5 (3.3) years, there were 169 (18%) cardiac deaths and 86 (9%) non-fatal infarctions. Multivariable Cox regression analysis showed age (hazard ratio (HR) 1.1, 95% confidence interval (CI) 1.02 to 1.05), previous myocardial infarction (HR 1.4, 95% CI 1.1 to 2.0), and number of ischaemic segments during the test (HR 2.0, 95% CI 1.0 to 3.7) as independent predictors of cardiac death and myocardial infarction. For every additional ischaemic segment there was a twofold increment in risk of late cardiac events. The annual cardiac death or myocardial infarction rate was 3.0% in patients with symptomatic ischaemia and 4.6% in patients with silent ischaemia (p < 0.01). Silent induced ischaemia was an independent predictor of cardiac death and myocardial infarction (HR 1.7, 95% CI 1.1 to 2.0). During follow up symptomatic patients were treated more often with cardioprotective therapy (p < 0.01) and coronary revascularisation (145 of 288 (50%) v 174 of 643 (27%), p < 0.001). CONCLUSIONS: Patients with silent ischaemia had a similar extent of myocardial ischaemia during DSE compared to patients with symptomatic ischaemia but received less cardioprotective treatment and coronary revascularisation and experienced a higher cardiac event rate.

The new clinical trials on pharmacological treatment in pulmonary arterial hypertension.

Past medical therapy for pulmonary arterial hypertension included the use of calcium-channel antagonists in acute vasoreactive subjects and oral anticoagulants and continuous intravenous administration of epoprostenol in the more severe cases. Recently, the thromboxane inhibitor terbogrel, the prostacyclin analogues treprostinil, beraprost and iloprost, and the endothelin receptor antagonist bosentan have been tested in clinical trials in >1,100 patients. Except for terbogrel, all compounds improved the mean exercise capacity by different degrees, as assessed by the 6-min walk test. In the evaluation of the clinical relevance of exercise capacity improvements, additional elements need to be considered, such as baseline functional class and concomitant favourable effects on combined clinical events (including hospitalisations, mortality and rescue therapies), quality of life and haemodynamics. No trials have shown effects on mortality, as the study protocols were not designed for assessing this end-point. Each new compound presents side-effects that are unpredictable in the individual patient and require appropriate attention upon treatment initiation and maintenance. These new therapeutic options will be available in the near future and will allow tailoring of the most appropriate treatment to the single patient, according to an individualised benefit-to-risk ratio.

[Implantable defibrillators and prevention of sudden death: clinical and economic implications in the light of the MADIT II study]. / Defibrillatori impiantabili e prevenzione della morte improvvisa: implicazioni cliniche ed economiche alla luce dello studio MADIT II.

The cardioverter-defibrillator is the most effective strategy to prevent sudden death in patients with previous episodes of ventricular tachyarrhythmia (secondary prevention of sudden death). In recent years the possibility of primary prevention of sudden death in selected groups of high risk patients has raised great interest. The MADIT II study highlighted the possibility of preventing sudden death in patients with coronary artery disease. According to this trial, identification of such patients can be performed by means of few clinical data and without expensive screenings (i.e. electrophysiological study). Indeed, patients with a previous myocardial infarction and low left ventricular ejection fraction (< 30%) may benefit from the implant of a cardioverter-defibrillator, with a reduction of the mortality risk by about 31% in the following two years. In the light of these data, implant of a cardioverter-defibrillator should be proposed in such patients, even if the problem of limited economic resources to meet the cost of the devices has to be considered even in the richest country of the world. Despite the positive scientific result, MADIT II has raised the problem of the effective possibility of adopting this therapeutic strategy in clinical practice and this question is still open. Strategies to reduce the theoretically high costs implicated by the MADIT II study include a reduction in the cost of defibrillators through dynamic market forces, the identification of subgroups at higher risk of sudden death, and the use of cheap defibrillators with limited diagnostic and therapeutic options. A long-term evaluation of the cost-effectiveness for western countries of these strategies is necessary to identify in which patient subgroups implant of a cardioverter-defibrillator is acceptable, i.e. cost-effective, in terms of primary prevention.

Folate supplementation after heart transplantation: effects on homocysteine plasma levels and allograft vascular disease.

BACKGROUND AND AIMS: After heart transplantation, the effects of folate supplementation on total homocysteine plasma levels (THcy) and heart allograft vascular disease (AVD) remain unclear. METHODS: Accordingly, we prospectively analyzed 48 heart transplant receipients referred for routine follow-up from July to September 1998 (age 54+/-11 years, 75% male, 35+/-27 months from transplant). Among these patients, 17 were treated with folate supplementation for 12 months (Group F), while 31 cross-matched for age, gender, serum creatinine and time from transplant (P>0.3 vs Group F for all) did not assume folate supplementation (Group NF). Routine coronary angiography for AVD detection was routinely obtained in every patient. RESULTS: THcy overall increased during the study period (from 16.6+/-6.5 to 19.4+/-7.6 micromol/l, P<0.001), and a strong trend toward higher THcy was observed in patients presenting AVD (22.4+/-8.7 vs 17.6+/-6.8 micromol/l, P=0.051). After 12 months THcy was lower in Group F as compared to Group NF (16.2+/-5.6 vs 21.1+/-8.1 micromol/l, respectively, P=0.033). CONCLUSIONS: Our results demonstrate that THcy increases over time in heart transplant recipients, and a strong trend toward higher THcy is observed in the presence of AVD. Since folate supplementation appears to positively influence THcy, a favorable effect of folate on AVD can be hypothesized.

Atrial fibrillation recurrence after internal cardioversion: prognostic importance of electrophysiological parameters.

OBJECTIVE: To evaluate the clinical and electrophysiological determinants of arrhythmia recurrence in patients undergoing internal atrial cardioversion for chronic atrial fibrillation (AF). SETTING: Tertiary cardiac referral centre. METHODS: 101 consecutive patients with failed external cardioversion or AF > or = 1 year underwent internal atrial cardioversion; once stable sinus rhythm (SR) was obtained, electrophysiological study was performed in 73 patients (72%) who gave informed consent. Patients were then followed on antiarrhythmic treatment. RESULTS: 101 consecutive patients underwent internal atrial cardioversion in the period 1996-1999 with 100% conversion to SR; prophylactic antiarrhythmic treatment was flecainide (52%), amiodarone (37%), and sotalol (11%). Average follow up at first AF recurrence was 18.4 (14.4) months (range 0.1-49.8 months); persistence of SR was observed in 72/101 (72%) patients. By logistic regression, AF duration (odds ratio (OR) 1.07, 95% confidence interval (CI) 1.01 to 1.13) and a lower sinus rate at discharge on antiarrhythmic drugs (OR 0.92, 95% CI 0.85 to 0.99) were independent predictors of AF recurrence, whereas age, New York Heart Association functional class, left atrial dimensions, and left ventricular ejection fraction were not predictive of arrhythmia recurrence. When electrophysiological parameters were added to the statistical model in 73 patients, a shorter atrial effective refractoriness (OR 1.04, 95% CI 1 to 1.08) and an abnormal relation of atrial effective refractoriness to cycle length (OR 31, 95% CI 3.7 to 266) were also independent predictors of AF recurrence at follow up, beyond AF duration and heart rate at discharge. CONCLUSIONS: Patients with failed external cardioversion or long lasting AF may benefit from internal atrial cardioversion and antiarrhythmic treatment to keep SR at long term; electrophysiological study may identify patients at the highest risk of arrhythmia recurrence. Although preservation of SR seems unlikely for AF duration > 3 years, a consistent minority of this subgroup (38%) may benefit from this approach.